Differences in the evolution of urban and rural surface thermal environment and their responses to urban renewal in Shanghai, China.

The rapid and extensive urbanization has profound impacts on urban thermal environment. It is of great significance to comprehensively understand how urbanization affects the evolution of urban thermal environment for urban ecological safety, environmental quality, and residents' health. Based on daily land surface temperature (LST) products of MODIS Aqua satellite in the summer of 2002-2020, we investigated the evolution of urban-rural differences in surface summer thermal environment in Shanghai during 2002-2020 and its response to urban spatial renewal. We used normalized land surface temperature (NLST) and urban heat island ratio index (URI) as the surface thermal environment measurement indicators, by combining vegetation index and impervious surface cove-rage, and used M-K trend analysis and interpretation analysis. The results showed that the linear growth rate of LST in Shanghai was 0.09 ℃·a-1 (2002-2020), and that URI showed a trend of first increasing (2002-2010) and then decreasing (2010-2020). The mean summer LST was generally in the order of urban core>suburban>rural. 1.6% of the areas showed a significant cooling trend, of which 54.0% were distributed in the urban core. 39.5% of the regions showed a significant warming trend, of which 77.6% were distributed in the suburban. In general, there were concentrated significant cooling areas in the highly urbanized urban areas, while there was a significant warming trend in the suburban. The transformation from urban expansion to urban renewal was the main reason for the emergence of concentrated and significant cooling areas in the urban. Nearly 20% of the urban area showed a signi-ficant increase of vegetation coverage. Urban renewal projects such as gathering vegetation or dispersing impervious surfaces in highly urbanized areas are important ways to effectively improve the urban residential thermal environment.

Host sex disparity and viral genotype dependence of the glycosylation level of small Hepatitis B surface protein in patients with HBeAg-positive chronic Hepatitis B.

BACKGROUND: Hepatitis B surface antigen (HBsAg) consists of six components of large/middle/small HBs proteins (L/M/SHBs) with non-glycosylated (ng)- or glycosylated (g)- isomers at sN146 in their shared S domain. g-SHBs plays a crucial role in hepatitis B virus (HBV) secretion. However, the host and viral factors impacting sN146 status in natural HBV infection remain revealed mainly due to the technical difficulty in quantifying g-SHBs and ng-SHBs in serum samples. METHODS: To establish a standardized Western blot (WB) assay (WB-HBs) for quantifying the SHBs isomers in serum samples of 328 untreated hepatitis B e antigen (HBeAg)-positive chronic hepatitis B (CHB) patients with genotype B or C HBV infection. The 1.3-mer HBV genotype B or C plasmids were transiently transfected into HepG2 cells for in vitro study. RESULTS: The median level of ng-SHBs was significantly higher than that of g-SHBs (N = 328) (2.6 vs. 2.0 log10, P < 0.0001). The median g-/ng-SHBs ratio in female patients (N = 75) was significantly higher than that of male patients (N = 253) (0.35 vs. 0.31, P < 0.01) and the median g-/ng-SHBs ratio in genotype C patients (N = 203) was significantly higher than that of the genotype B patients (N = 125) (0.33 vs. 0.29, P < 0.0001). CONCLUSIONS: Our findings suggest that the g-/ng-SHBs ratio is host-sex-biased and viral genotype dependent in treatment naïve patients with HBeAg-positive chronic hepatitis B, which indicates the glycosylation of SHBs could be regulated by both host and viral factors. The change of ratio may reflect the fitness of HBV in patients, which deserves further investigation in a variety of cohorts such as patients with interferon or nucleos(t)ide analogues treatment.

Vegetation growth enhancement modulated by urban development status.

Cities are natural laboratories for studying the vegetation response to global change due to their own climatic, atmospheric, and biological conditions. However, whether the urban environment promoted vegetation growth is still uncertain. Using the Yangtze River Delta (YRD), an economic powerhouse of modern China, as a case study, this paper investigated the impact of urban environment on vegetation growth at three scales: cities, sub-cities (rural-urban gradient) -pixels. Based on the satellite observations of vegetation growth indicated during 2000-2020, we explored the direct (replacement of original land by impervious surfaces) and indirect impact (e.g., climatic environment) of urbanization on vegetation growth and their trends with urbanization level. We found that significant greening accounted for 43.18 %, and significant browning accounted for 3.60 % of the pixels in the YRD. Urban area was turning green faster than suburban area. Moreover, land use change intensity (D) was a representation of the direct impact ωd of urbanization. The direct impact of urbanization on vegetation growth was positively correlated with the intensity of land use change. Furthermore, vegetation growth enhancement due to indirect impact ωi occurred in 31.71 %, 43.90 % and 41.46 % of the YRD cities in 2000, 2010 and 2020. And vegetation enhancement occurred in 94.12 % of highly urbanized cities in 2020, while in medium and low urbanization cities, the averaged indirect impact was near zero or even negative, proving that vegetation growth enhancement was modulated by urban development status. Also, the growth offset (τ) was most pronounced in high urbanization cities (4.92 %), but there was no growth compensation in medium urbanization cities (-4.48 %) and low urbanization cities (-57.47 %). When urbanization intensity reached a threshold value of 50 % in highly urbanized cities, the growth offset (τ) tended to saturate and remained unchanged. Our findings have important implications for understanding the vegetation response to continuing urbanization process and future climate change.

The enhancement role of Matrigel on HBV infection in HepG2-NTCP cells.

The hepatoma cell lines stably expressing sodium taurocholate cotransporting polypeptide (NTCP), the receptor of hepatitis B virus (HBV) infection, serve as important infection models for studying viral biology and drug discovery. However, the efficiency of infection greatly varies. In this study, we studied the effects and potential mechanisms of Matrigel® hESC-qualified (M-hq), a biological basement membrane matrix commonly used in cell culture, on promotion HBV in vitro infection in HepG2-NTCP cells. For the first time, our findings demonstrate that M-hq could enhance the infection efficiency of cell culture-derived HBV with no impact on the cell viability, the HBV transcription and response to antiviral treatments. The infection enhancement is reproducible and is suggested to occur at HBV attachment step. Our study suggests that this novel system is applicable for studying HBV biology and new drugs.

A Review of the Current Status of Clinical Management of COVID-19 in the Elderly.

The high infectivity and severity of SARS-CoV-2 infection (COVID-19), and our limited understanding of the biology of the novel coronavirus, as well as the lack of an effective treatment for COVID-19, have created a global pandemic. Those most likely to become seriously ill with COVID-19 are adults, especially the elderly and those who are already weak or sick. At present, a specific drug for treatment of COVID-19 has not been developed. This, combined with the typical coexistence of a variety of chronic diseases in elderly patients, makes treatment challenging at present. In addition, for elderly patients, COVID-19 isolation measures during the epidemic can easily lead to psychological problems. Thus, how to manage elderly patients has become a focus of social attention in the current circumstances. This article reviews the effects of COVID-19 and makes management suggestions for elderly patients during this epidemic period. In addition to the elderly, critically ill people are also highly susceptible to this novel coronavirus. For elderly COVID-19 patients, antiviral therapy, immune regulation, and even auxiliary respiratory therapy can be given after a comprehensive evaluation of the disease. With the approval and use of COVID-19 vaccines, it is reasonable to expect that we can conquer SARS-CoV-2.

Iron down-regulates leptin by suppressing protein O-GlcNAc modification in adipocytes, resulting in decreased levels of O-glycosylated CREB.

We previously reported that iron down-regulates transcription of the leptin gene by increasing occupancy of phosphorylated cAMP response element-binding protein (pCREB) at two sites in the leptin gene promoter. Several nutrient-sensing pathways including O-GlcNAcylation also regulate leptin. We therefore investigated whether O-glycosylation plays a role in iron- and CREB-mediated regulation of leptin. We found that high iron decreases protein O-GlcNAcylation both in cultured 3T3-L1 adipocytes and in mice fed high-iron diets and down-regulates leptin mRNA and protein levels. Glucosamine treatment, which bypasses the rate-limiting step in the synthesis of substrate for glycosylation, increased both O-GlcNAc and leptin, whereas inhibition of O-glycosyltransferase (OGT) decreased O-GlcNAc and leptin. The increased leptin levels induced by glucosamine were susceptible to the inhibition by iron, but in the case of OGT inhibition, iron did not further decrease leptin. Mice with deletion of the O-GlcNAcase gene, either via whole-body heterozygous deletion or through adipocyte-targeted homozygous deletion, exhibited increased O-GlcNAc levels in adipose tissue and increased leptin levels that were inhibited by iron. Of note, iron increased the occupancy of pCREB and decreased the occupancy of O-GlcNAcylated CREB on the leptin promoter. These patterns observed in our experimental models suggest that iron exerts its effects on leptin by decreasing O-glycosylation and not by increasing protein deglycosylation and that neither O-GlcNAcase nor OGT mRNA and protein levels are affected by iron. We conclude that iron down-regulates leptin by decreasing CREB glycosylation, resulting in increased CREB phosphorylation and leptin promoter occupancy by pCREB.

Downregulation of intrinsic apoptosis pathway in erythroblasts contributes to excessive erythrocytosis of chronic mountain sickness.

Chronic mountain sickness (CMS) has a higher incidence in the plateau region and is characterized by excessive erythrocytosis and hypoxemia. Bcl-2 family plays an important role in the process of erythropoiesis and the regulation of apoptosis. This study aimed to examine the change in apoptosis of erythroblasts in CMS patients and explore the involvement of Bcl-2 family. Bone marrow mononuclear cells (BMMNCs) were isolated by density gradient centrifugation from 18 CMS patients and 17 control participants. The apoptotic rate, mitochondrial membrane potential (MMP), the protein expression of caspase-3, TNFR, Fas, Bcl-2, Bax and Cyt-C were examined by flow cytometry, and mRNA expression was determined by real-time PCR. The results showed that apoptotic rate of erythroblasts was lower and MMP was higher in CMS group than in control group. The mRNA and protein expression levels of Bcl-2 were higher while Bax level was lower in CMS group than in control group. In CMS group, the apoptosis rate of CD71+ erythroblasts was negatively correlated with the ratio of CD71+ cells in BMMNCs and positively correlated with hemoglobin level. In conclusion, erythroblasts apoptosis is decreased due to the regulation of the expression of Bcl-2 family members in the erythroblasts of CMS patients.

Impacts of HBV rtH55R polymerase substitution on viral replication and rtM204I/V resistance to nucleoside/nucleotide antiviral drugs.

BACKGROUND: High genetic variability at the reverse transcriptase (RT) region of HBV could confer resistance to nucleoside/nucleotide analogues (NUCs). The aim of this study was to identify new RT amino acid (AA) substitutions related to NUC resistance. METHODS: HBV RT sequences of genotype C from 501 chronic hepatitis B (CHB) patients were analysed to identify potential RT substitutions related to NUC resistance. In vitro studies without and with NUCs were performed in a HepG2 cell line transfected by clones with RT harbouring wild-type or substituted AA(s) of interest. RESULTS: Among 261 NUC-treated CHB patients, we found a high detection rate of rtM204I/V substitution (30.7% [80/261]). We identified a new substitution of rtH55R, and its detection rate had a significantly increasing trend from 3.8% (9/240) in the untreated group to 7.2% (13/181) or 33.8% (27/80) in the treated group with rtM204 or with rtM204I/V substitutions (P<0.0001). In vitro studies showed that rtH55R had a similar HBV DNA level compared to wild type. The rtH55R+rtM204I clone had a significantly better replication capacity than the rtM204I clone without NUCs (P<0.05). The replication capacity of the rtM204I clone was found to significantly decrease under lamivudine treatment, but this was not found in the rtH55R+rtM204I clone. CONCLUSIONS: We identified a new HBV RT substitution of rtH55R in genotype-C-infected CHB patients. It is frequently found in combination with rtM204I/V substitution under NUC treatment. In vitro studies suggest that it might play some replication compensatory role in rtM204I mutants under lamivudine treatment.

PI3K-Akt Signal Transduction Molecules Maybe Involved in Downregulation of Erythroblasts Apoptosis and Perifosine Increased Its Apoptosis in Chronic Mountain Sickness.

BACKGROUND Chronic mountain sickness (CMS) has a higher incidence in the plateau region. The one of its principal characters is excessive erythrocytosis. The PI3K-Akt pathway plays an important role in the process of erythropoiesis, and could downregulate apoptosis by regulating apoptosis-related molecules. In this paper, we explored the change in apoptosis of erythroblasts and the effect of the PI3K-Akt signal pathway on erythroblasts apoptosis in CMS. MATERIAL AND METHODS A total of 22 CMS and 20 non-CMS participants were involved in this study. Bone marrow mononuclear cells were cultured and treated with celecoxib and perifosine in vitro for 72 hours. The apoptotic rate, the mRNA expressions of Akt, Bcl-xl, and caspase-9, and the protein expressions of Akt, p-Akt, Bcl-xl, and caspase-9 were determined by flow cytometry, quantitative RT-PCR, and western-blot technique. RESULTS The apoptotic rate of cultured erythroblasts was lower in the CMS group than in the non-CMS group. It was increased after perifosine intervention. The mRNA and protein expressions of Akt and Bcl-xl were higher and caspase-9 was lower in the CMS group than the non-CMS group. Perifosine induced decreased Bcl-xl mRNA and proteins and p-Akt proteins, and increased caspase-9 mRNA and proteins in vitro. In the CMS group, the hemoglobin concentration was correlated with apoptotic rate negatively and with Bcl-xl mRNA positively in erythroblasts; the erythroblasts apoptotic rate was negatively associated with the Akt mRNA and Bcl-xl mRNA. CONCLUSIONS The erythroblasts apoptosis was downregulated and the PI3K-Akt signal pathway appeared to be involved in the mechanism of decreased erythroblasts apoptosis in CMS.

Amino acid similarities and divergences in the small surface proteins of genotype C hepatitis B viruses between nucleos(t)ide analogue-naïve and lamivudine-treated patients with chronic hepatitis B.

Entire C-genotype small hepatitis B surface (SHBs) sequences were isolated from 139 nucleos(t)ide analogues (NA)-naïve and 74 lamivudine (LMV)-treated chronic hepatitis B (CHB) patients. The conservation and variability of total 226 amino acids (AAs) within the sequences were determined individually, revealing significant higher mutant isolate rate and mutation frequency in LMV-treated cohort than those in the NA-naïve one (P=0.009 and 0.0001, respectively). Three absolutely conserved fragments (s16-s19, s176-s181 and s185-s188) and seven moderately conserved regions (a few AA sites acquiring increased variability after LMV-treatment) were identified. The significant mutation rate increase after LMV-treatment occurred primarily in major hydrophilic region (except 'a' determinant) and transmembrane domain 3/4, but not in other upstream functional regions of SHBs. With little influence on immune escape-associated mutation frequencies within 'a' determinant, LMV-monotherapy significantly induced classical LMVr-associated mirror changes sE164D/rtV173L, sI195M/rtM204V and sW196L/S/rtM204I, as well as non-classical ones sG44E/rtS53N, sT47K/A/rtH55R/Q and sW182stop/rtV191I outside 'a' determinant. Interestingly, another newly-identified truncation mutation sC69stop/rtS78T decreased from 7.91% (11/139) in NA-naïve cohort to 2.70% (2/74) in LMV-treated one. Altogether, the altered AA conservation and diversity in SHBs sequences after LMV-treatment in genotype-C HBV infection might shed new insights into how LMV-therapy affects the SHBs variant evolution and its antigenicity.

Hepatitis B virus basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

The present study was aimed to obtain baseline information of basal core promoter A1762T/G1764A and precore G1896A mutations of hepatitis B virus (HBV) in 192 HBeAg-positive chronically-infected Chinese patients, who were potential candidates for antiviral treatment. The detection of these mutations (including minor mutant subpopulations) was achieved by direct sequencing, whose sensitivity for minor mutant subpopulations identification was confirmed by clone sequencing. Patients enrolled were infected with either genotype B (46.35%) or C (53.65%) HBV identified by routine tests in our laboratory. The A1762T/G1764A or G1896A mutations were detected in 125specimens (125/192, 65.10%), in which 77 (77/125, 61.60%) existed as subpopulations. The A1762T/G1764A mutations were found to be more prevalent in genotype C than that in genotype B HBV [62.14% (64/103) vs. 20.22% (18/89), P<0.0001]. There is no statistically significant link between G1896A and genotypes. The emergence of A1762T/G1764A mutations was also found to be associated with an older age, an elevated ALT/AST level, and a lower HBsAg level in serum [wild-type vs. mutant: 4.57 (3.46-5.42) vs. 3.93 (2.51-5.36), P<0.0001]. In conclusion, HBV basal core promoter mutations A1762T/G1764A are associated with genotype C and a low serum HBsAg level in chronically-infected HBeAg-positive Chinese patients.

[The value of determination of serum myoglobin in estimation of degree of illness and prognosis of patients with sepsis in Xining area].

OBJECTIVE: To investigate the value of determination of serum myoglobin (MYO) in estimation of the degree of illness and prognosis of patients with sepsis in Xining area. METHODS: Serum MYO was measured and acute physiological and chronic health estimationII (APACHEII) score was evaluated in 30 cases with sepsis within 24 hours of admission to emergency intensive care unit (EICU), and their correlation was analyzed. The patients were divided into two groups, survival group and death group according to the result within 28 days. The MYO and APACHEII score were analyzed in both groups. All cases were divided into three groups: namely <500 (n=10), 500-1 000 (n=14), >1 000 µg/L (n=6) groups, according to serum MYO value, and APACHEII score and dead case were compared among three groups. RESULTS: Sixteen patients survived, and 14 patients died. The level of serum MYO and APACHEII score were significantly lower in survival group than death group [MYO (µg/L): 607.85±499.40 vs. 976.21±370.10, APACHEII score: 15.50±4.43 vs. 18.93±3.63, t(1)=2.28, t(2)=2.29, both P<0.05]. With the elevation of serum MYO, the dead case was increased in sepsis patients (the dead case in MYO<500, 500-1 000, >1 000 µg/L groups was 2, 7, 5 cases, respectively,χ(2)=5.94, P<0.05), but there was no difference in APACHEII score among three groups. There was significant positive correlation between serum MYO and APACHEII score (r=0.407, P<0.05). CONCLUSION: Determination of serum MYO can reflect degree of illness and prognosis of sepsis patients in Xining area.